Atazanavir Dosage Form and Label Changes

The FDA has approved a new pediatric dosage form and label changes for atazanavir. Please see the FDA announcement for more information.

Search Term

Guideline Search

Type your search term(s) in the text box. Users can only search one guideline at a time. To search for an exact phrase, use quotation marks (i.e. "what to start"). To narrow your search, add additional relevant terms. If you are not finding what you need, try searching similar terms (i.e. perinatal OR pregnancy) to broaden your search.

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

The major use of ritonavir is as a PK enhancer of other protease inhibitors (PIs) used in pediatric patients and in adolescents and adults. The recommended dose of ritonavir varies and is specific to the drug combination selected. See dosing information for specific PIs.

In the Unusual Situation When Ritonavir is Prescribed as Sole PI:

See manufacturer guidelines.

Selected Adverse Events

Gastrointestinal (GI) intolerance, nausea, vomiting, diarrhea

Paresthesia (circumoral and extremities)

Hyperlipidemia, especially hypertriglyceridemia

Hepatitis

Asthenia

Taste perversion

Hyperglycemia

Fat maldistribution

Possible increased bleeding episodes in patients with hemophilia

Toxic epidermal necrolysis and Stevens-Johnson syndrome

Special Instructions

Administer ritonavir with food to increase absorption and reduce GI side effects.

If ritonavir is prescribed with didanosine, administer the drugs 2 hours apart.

Refrigerate ritonavir capsules only if the capsules will not be used within 30 days or cannot be stored below 77° F (25° C). Ritonavir tablets are heat stable.

Do not refrigerate ritonavir oral solution; store at room temperature (68–77° F or 20–25° C). Shake the solution well before use.

Ritonavir oral solution has limited shelf life; use within 6 months.

Patients who have persistent or significant nausea with the capsule may benefit from switching to the tablet. Also, the tablet is smaller than the capsule and thus easier to swallow.

Dosing of ritonavir in patients with hepatic impairment: Ritonavir is primarily metabolized by the liver. No dosage adjustment is necessary in patients with mild or moderate hepatic impairment. Data are unavailable on ritonavir dosing for adult or pediatric patients with severe hepatic impairment. Use caution when administering ritonavir to patients with moderate-to-severe hepatic impairment.

Resistance to ritonavir is not clinically relevant when the drug is used as a pharmacokinetic enhancer of other protease inhibitors (PIs).

Pediatric Use

Approval
Ritonavir has been approved by the Food and Drug Administration (FDA) for use in the pediatric population.

Efficacy: Effectiveness in Practice
Use of ritonavir as the sole PI in combination antiretroviral therapy (cART) in children is not recommended. Although ritonavir has been well studied in children, its use as a sole PI for therapy is limited because ritonavir is associated with a higher incidence of gastrointestinal toxicity and has a greater potential for drug-drug interactions than other PIs. Also, ritonavir as a sole PI is associated with a higher risk of virologic failure than efavirenz or ritonavir-boosted lopinavir.3-5 In addition, poor palatability of the liquid preparation and large pill burden with the capsules (adult dose is six capsules or tablets twice daily) limit its use as a sole PI. Concentrations are highly variable in children younger than aged 2 years, and doses of 350 to 450 mg/m2 twice daily may not be sufficient for long-term suppression of viral replication in this age group.6-14 However, in both children and adults, ritonavir is recommended as a PK enhancer to boost the second PI in an ART regimen. Ritonavir acts by inhibiting the metabolism of the second (boosted) PI by the liver, thereby increasing the plasma concentration of the second (boosted) PI.

Dosing
Pediatric dosing regimens including boosted fosamprenavir, tipranavir, darunavir, atazanavir and a PI co-formulation, ritonavir-boosted lopinavir, are available (see individual PIs for more specific information).
Toxicity
Full-dose ritonavir has been shown to prolong the PR interval in a study of healthy adults who were given ritonavir at 400 mg twice daily.2 Potentially life-threatening arrhythmias in premature newborn infants treated with ritonavir-boosted lopinavir have been reported; thus, ritonavir-boosted lopinavir should not be used in this group of patients.15,16 Co-administration of ritonavir with other drugs that prolong the PR interval (e.g., macrolides, quinolones, methadone) should be undertaken with caution because it is unknown how co-administering any of these drugs with ritonavir will affect the PR interval. In addition, ritonavir should be used with caution in patients who may be at increased risk of developing cardiac conduction abnormalities, such as those with underlying structural heart disease, conduction system abnormalities, ischemic heart disease, or cardiomyopathy.

Taylor BS, Hunt G, Abrams EJ, et al. Rapid development of antiretroviral drug resistance mutations in HIV-infected children less than two years of age initiating protease inhibitor-based therapy in South Africa. AIDS Res Hum Retroviruses. Sep 2011;27(9):945-956. Available at http://www.ncbi.nlm.nih.gov/pubmed/21345162.